Prognostic relevance of C-terminal Mdm2 detection is enhanced by p53 positivity in soft tissue sarcomas.
We examined the clinical value of immunohistochemical (IHC) Mdm2 detection by an N-terminal (IF2) and a C-terminal (19E3) binding monoclonal antibody (Ab) in soft tissue sarcomas (STSs) with regard to the p53 status. Therefore, we investigated a cohort of 198 patients with STSs of six entities with known p53 IHC by using a multivariate Cox regression model to determine the prognostic value of Mdm2 staining. Only positivity with the 19E3 Ab correlated multivariately significantly with survival (RR = 2.32, p = 0.0035). We stratified the C-terminal Mdm2 staining (19E3) according to p53 IHC (DO-1) and found patients could be divided into three groups with an increasing risk: (a) patients with Mdm2 (19E3)-negative as well as p53 (DO-1)-negative tumors, (b) patients with tumors that were either Mdm2 (19E3) or p53 (DO-1) positive, and (c) patients with tumors that were Mdm2 (19E3) as well as p53 (DO-1) positive. Positive staining for both Mdm2 and p53 meant a very poor prognosis with a relative risk of 4.63 (p = 0.00001). This points to the possibility that--in addition to the p53-dependent pathway--Mdm2 could have an effect through a p53-independent pathway. Thus, our results indicate that C-terminal Mdm2 staining (19E3) constitutes an independent prognostic marker in STS.
Würl
P
P
Clinic of General Surgery, Martin Luther University of Halle-Wittenberg, Halle/Saale, Germany.
Meye
A
A
Berger
D
D
Bache
M
M
Lautenschläger
C
C
Schmidt
H
H
Kalthoff
H
H
Rath
F W
FW
Taubert
H
H
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D011379:Prognosis; D016016:Proportional Hazards Models; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D051736:Proto-Oncogene Proteins c-mdm2; D012509:Sarcoma / Q000737:chemistry* / Q000473:pathology / Q000628:therapy; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*
D014408:Biomarkers, Tumor; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2